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Publication : In vivo regulation of the mouse beta myosin heavy chain gene.

First Author  Knotts S Year  1994
Journal  J Biol Chem Volume  269
Issue  49 Pages  31275-82
PubMed ID  7983072 Mgi Jnum  J:20280
Mgi Id  MGI:69625 Doi  10.1016/s0021-9258(18)47419-4
Citation  Knotts S, et al. (1994) In vivo regulation of the mouse beta myosin heavy chain gene. J Biol Chem 269(49):31275-82
abstractText  The interactions of trans-acting factors with their respective cis-acting elements in the 5' upstream region of the beta myosin heavy chain gene (MyHC) regulate its tissue- and developmental stage-specific expression. The role of three conserved elements, an MCAT or TEF-1 binding site, a C-rich region, and a beta e3 region, in muscle-specific gene expression was analyzed in vivo. Each cis-acting site was ablated in the context of the beta MyHC promoter, fused to the chloramphenicol acetyltransferase reporter gene, and used to generate transgenic mice. In contrast to results obtained in vitro, the data demonstrate that mutating any one of these cis-acting elements does not affect the level or tissue specificity of transgene expression. Sequences upstream of -600 can functionally substitute for any one of these regulatory cassettes and are important both for high levels of expression as well as for controlled muscle specificity. Mutation of any two of the cis-acting elements also does not affect transgene expression. However, simultaneous mutation of the three sites significantly reduces expression, indicating that these conserved sequences do play an important role and that combinatorial interactions underlie the beta MyHC's regulation.
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